title: The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM.
  
  
  METHODS
  In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses.
  
  
  RESULTS
  DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p < 0.05). Clinical characteristics and echocardiographic parameters assessing LV morphology were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all p < 0.001). Multivariate regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001).
  
  
  CONCLUSIONS
  An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM.
authors.affiliation: Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain. sravassa@unav.es.
authors.forename: Susana
authors.initials: S
authors.lastname: Ravassa
authors.forename: Joaquín
authors.initials: J
authors.lastname: Barba
authors.forename: Isabel
authors.initials: I
authors.lastname: Coma-Canella
authors.forename: Ana
authors.initials: A
authors.lastname: Huerta
authors.forename: Begoña
authors.initials: B
authors.lastname: López
authors.forename: Arantxa
authors.initials: A
authors.lastname: González
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism*; D006321:Heart / Q000294:innervation*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D064231:Nestin / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis
chemical_list: D019922:GAP-43 Protein; C577486:Nes protein, rat; D064231:Nestin